Journal article
Potency of siRNA versus shRNA mediated knockdown in vivo
Journal of pharmaceutical sciences, Vol.96(11), pp.2922-2930
11/2007
DOI: 10.1002/jps.20968
PMID: 17518360
Abstract
The intracellular delivery of small interfering RNA (siRNA) is a therapeutic strategy to transiently block gene expression. Two silencing RNA strategies utilize either synthetic double stranded RNA or plasmid DNA encoding a short hairpin RNA (shRNA). In the present study, we have quantitatively compared the potency of siRNA (siLuc1) and shRNA (pShagLuc) mediated knockdown of luciferase expression in vivo using hydrodynamic dosing and bioluminescence imaging (BLI). Following hydrodynamic coadministration of siLuc1 or pShagLuc with a plasmid encoding luciferase (pGL3), mice were analyzed for transgene expression by BLI. The knockdown of luciferase expression by siLuc1 or pShagLuc was observed at 3 h and persisted for 3 days. The potency of siLuc1 and pShagLuc was equivalent with maximal effect at 10 microg coadministered with 1 microg of pGL3 resulting in >80% knockdown. Combined dosing of siLuc1 and pShagluc (5 microg each) with 1 microg of pGL3 resulted in >99% knockdown. Analysis of the data established that shRNA was significantly more potent than siRNA at mediating knockdown when compared on a mole basis. The combination of hydrodynamic dosing and BLI to measure siRNA or shRNA mediated knockdown of luciferase provide an attractive in vivo quantitative method to test formulations that target the liver.
Details
- Title: Subtitle
- Potency of siRNA versus shRNA mediated knockdown in vivo
- Creators
- Marie A McAnuff - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USAGarrett R RettigKevin G Rice
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.96(11), pp.2922-2930
- DOI
- 10.1002/jps.20968
- PMID
- 17518360
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- United States
- Grant note
- DK063196 / NIDDK NIH HHS DK066212 / NIDDK NIH HHS T32 GM067795 / NIGMS NIH HHS
- Language
- English
- Date published
- 11/2007
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065690802771
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